The long-term objective of this project is to completely understand the processes involved in implantation of the blastocyst in the endometrium. Implantation is one of the major transition stages of pregnancy. Because of the sequestered position and species peculiarities, our understanding of the cellular interactions between trophoblast and endometrium lag behind our understanding of the hormonal aspects necessary for its initiation. Nevertheless both from the point of view of understanding normal development and in our search for events that may be regulated without altering other aspects of the organism, we need to understanding the unique features of this process. Formation and maturation of the preimplantation embryo will be studied by transmission electron microscopy of baboon and rhesus monkey morulae and blastocysts. The role of endocytosis in blastocyst-endometrial relationships will be investigated with tracers of fluid-phase and receptor-mediated uptake. The fate of interiorized material, evidence of transport and membrane recycling will be followed using principally rat blast-ocysts, for development of the methods, and primate blastocysts to confirm the presence of comparable pathways. The response of the primate endometrium to trophoblast and the mechanism by which trophoblast spreads within the endometrium will be compared in rhesus monkey and baboon using transmission and scanning electron microscopy. In vitro models of implantation will be developed using rat and guinea pig blastocysts to compare invasiveness of trophoblast, and the way in which it penetrates complex substrates such as corneal stroma, matrix formed by smooth muscle cells and basal laminas. Culture of these blastocysts on a columnar epithelium will be used to study the mechanisms by which trophoblast penetrates epithelial cell layers. Baboon blastocysts will be used with the best of the models developed.